The molecular biology of tumor metastasis has been investigated. A model system consisting of seven related murine K1735 melanoma cell lines which vary in metastatic potential was used for study. A cDNA probe, pNM23, recognizes two RNA species which are expressed to a greater extent in RNA of low metastatic K1735 cell lines than in related higher metastatic K1735 cell lines. The restriction map and DNA sequence of this cDNA were obtained. Computer analysis of the predicted amino acid sequence of the only open reading frame indicates that the NM23 gene encodes a novel protein. In contrast, a cDNA probe to the basement membrane protein type IV collagen recognizes RNAs more abundant in highly metastatic K1735 cell lines than in related, low metastatic cell lines. Synthesis and secretion of type IV collagen and other basement membrane components, laminin and entactin, are relatively increased in highly metastatic K1735 cell lines. Cellular analysis of K1735 melanoma metastatic potential determined that potential to invade basement membranes and factors involved in colonization are critical to observed differences in K1735 melanoma metastatic potential; cellular sensitivity to host immune responses were not a determining factor. Metastases in this model system can therefore be associated with changes in activity of specific genes. Planned experiments will determine the diagnostic and therapeutic potential of these cDNA probes.